Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

ABC transporters are integral membrane proteins which couple the energy of ATP hydrolysis to the translocation of solutes across cell membranes. BtuCD is a approximately 1100-residue protein found in the inner membrane of Gram-negative bacteria which transports vitamin B12. Vitamin B12 is bound in the periplasm by BtuF, which delivers the solute to the periplasmic entrance of the transporter protein complex BtuCD. Molecular dynamics simulations of the BtuCD and BtuCDF complexes (in a lipid bilayer) and of the isolated BtuD and BtuF proteins (in water) have been used to explore the conformational dynamics of this complex transport system. Overall, seven simulations have been performed, with and without bound ATP, corresponding to a total simulation time of 0.1 micros. Binding of ATP drives closure of the nucleotide-binding domains (NBDs) in BtuD in a symmetrical fashion, but not in BtuCD. It seems that ATP constrains the flexibility of the NBDs in BtuCD such that their closure may only occur upon binding of BtuF to the complex. Upon introduction of BtuF, and concomitant with NBD association, one ATP-binding site displays a closure, while the opposite site remains relatively unchanged. This asymmetry may reflect an initial step in the "alternating hydrolysis" mechanism and is consistent with measurements of nucleotide-binding stoichiometries. Principal components analysis of the simulation of BtuCD reveals motions that are comparable to those suggested in current transport models.

Original publication




Journal article



Publication Date





2767 - 2778


ATP-Binding Cassette Transporters, Bacterial Proteins, Computer Simulation, Crystallography, X-Ray, Models, Molecular, Protein Conformation